This revised proposal seeks to test the hypothesis that defective sympatho-adrenal system (SAS) function is responsible for the development and maintenance of obesity, using genetic obesity (Zucker rats) and diet induced obesity in rats as two models of human obesity. Preliminary studies have documented defective SAS function in the obese Zucker rat although the physiologic and anatomic site of this abnormality is unknown. SAS function will be assessed in awake rats with right atrial cannulae by measuring stress evoked release of plasma catecholamines. Simultaneously obtained levels of glucose, insulin and glycerol will index the concomitant changes in carbohydrate and lipid metabolism. Turnover and levels of catecholamines will be correlated with changes in body weight and composition, food intake and in vitro brown adipose tissue oxygen consumption and Beta adrenergic receptor binding found during chronic fasting and chronic activation of the SAS in lean and obese Zucker rats to assess the way in which changes in SA activity might affect these parameters. The effect of diet induced obesity on SAS function will be used to assess the role of defective SAS function on the subsequent development of diet induced obesity inneonatal and adult rats. Other studies will assess the effect of fasting DIO rats on SAS function. These studies should ultimately provide the basis for the development of treatment for obesity based on manipulation of SAS function if defective SAS fnction is important in obesity.